Open AccessMolecular Genetic Analysis of HLA—DR and HLA—DQ Genes Among Anti—U1‐70‐kd Autoantibody Positive Connective Tissue Disease Patients
Author(s) -
Kaneoka Hidetoshi,
Hsu KouChing,
Takeda Yoshihiko,
Sharp Gordon C.,
Hoffman Robert W.
Publication year - 1992
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.1780350113
Subject(s) - autoantibody , human leukocyte antigen , polymerase chain reaction , epitope , immunology , haplotype , gene , biology , autoimmune disease , hla dq , antigen , microbiology and biotechnology , genetics , antibody , allele
Objective. We have recently found that the presence of autoantibodies against the 70‐kd polypeptide of U1 RNP (U1‐70‐kd) is associated with HLA—DR4 and DR2. To further characterize this association, we performed a molecular genetic analysis of HLA—DR and DQ genes among patients with autoantibodies against U1‐70‐kd. Methods. The polymerase chain reaction (PCR), sequence‐specific oligonucleotide hybridization, and solid‐phase direct DNA sequencing of PCR‐amplified DNA were utilized to analyze HLA—DRB1, DRB5, DQA1, and DQB1 genes. Results. A comprehensive analysis of HLA—DRB1, DRB5, DQA1, and DQB1 from 27 patients and controls identified shared amino acids FDYFYQA (Phe, Asp, Tyr, Phe, Tyr, Gln, Ala) at positions 26, 28, 30—32, 70, and 73 of HLA—DRB1 on disease‐associated haplotypes. Conclusion. A common cluster of shared amino acids, or a shared epitope, identified within HLA—DRB1 among anti—U1—70‐kd autoantibody positive connective tissue disease patients may be important in regulating an autoimmune response to the U1—70‐kd antigen.